Zero-Order Release of Gossypol Improves Its Antifertility Effect and Reduces Its Side Effects Simultaneously

Wen, Ning; Dong, Yansheng; Song, Rui; Zhang, Wenpeng; Sun, Chao; Zhuang, Xiaomei; Guan, Ying; Meng, Qingbin; Zhang, Yongjun

doi:10.1021/acs.biomac.7b01648

Cited by 27 publications

(22 citation statements)

References 40 publications

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“…As a result, the film absorbance increased with increasing dipping cycles, as shown in Figure 2A. Similar to other hydrogen-bonded LBL films reported previously, [25][26][27] the PEG-LEU/TA film showed an exponential growth pattern ( Figure 2B). Moreover, the thickness of the LBL films increased following the same pattern ( Figure 2C).…”

Section: Preparation Of the Filmssupporting

confidence: 86%

“…[21][22][23] When these films are fabricated from monodisperse polymers, zero-order release can be achieved. [24][25][26][27][28][29] Using this principle, dynamic LBL films of PEGylated leuprolide (PEG-LEU) and tannic acid (TA) were fabricated using dynamic hydrogen bonding as the driving force. Both in vitro and in vivo tests revealed that drug release from the film followed perfect zero-order kinetics.…”

Section: Introductionmentioning

confidence: 99%

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Hydrogen‐Bonded Films for Zero‐Order Release of Leuprolide

Zhuang²,

Zhang³

et al. 2020

Macromolecular Bioscience

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Leuprolide has been widely used in androgen deprivation therapy for the treatment of advanced prostate cancer, but its use is still limited due to its short half‐life. Herein, hydrogen‐bonded layer‐by‐layer films are fabricated from PEGylated leuprolide (PEG‐LEU) and tannic acid (TA). Because of its dynamic nature, the film disintegrates gradually in water and releases PEG‐LEU and TA. The in vitro release profile indicated perfect zero‐order kinetics, which is explained by the unique release mechanism. When implanted subcutaneously in male rats, the films maintain a constant serum drug level. For a 60‐bilayer film, the serum drug level is maintained constant for ≈24 days. No initial burst release is observed, suggesting that the in vivo release also follows zero‐order kinetics. Initially, an increase in the level of serum testosterone is induced by the released drug, followed by testosterone suppression to a constant level below the castrate level, which could be maintained as long as a constant serum drug level is maintained. Since the new drug carriers avoid an initial burst release of the drug and maintain a constant serum drug level and hence a constant serum testosterone level below the castrate level, these carriers are highly promising for androgen deprivation therapy.

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Section: Preparation Of the Filmssupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Hydrogen‐Bonded Films for Zero‐Order Release of Leuprolide

Zhuang²,

Zhang³

et al. 2020

Macromolecular Bioscience

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“…[8][9][10][11][12] A particularly challenging delivery mode is zero-order, in which the dose of the delivered drug is independent of time or residual concentration in the delivery vehicle. 4,[13][14][15] In general, zero-order release systems are technologically more difficult to create and therefore result in significantly higher prices. 16 Sophisticated examples of spherical drug vehicles like porous microspheres or polymer micelles have both proven to be capable of ensuring zero-or near zero-release behavior.…”

Section: Introductionmentioning

confidence: 99%

Glycerol–Silicone Elastomers as Active Matrices with Controllable Release Profiles

2018

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Drug release regimes must be controlled for the optimal therapeutic effect. Although it is relatively straightforward to create first-order release matrices, it can be challenging to avoid an initial burst. Matrices with zero-order profiles are perceived to be beneficial in many cases but are even more difficult to formulate. We describe the straightforward synthesis of elastomeric composites prepared from silicone in which the active substance is dispersed in glycerol. The release of glycerol-soluble actives from the films of these materials was shown to be tunable with respect to the order of release (zero- or first-order) simply by changing the glycerol content. Importantly, release from the elastomers showed no burst effect. The discrete glycerol domains embedded within a silicone matrix act as reservoirs for active substances. Upon contact with aqueous media, the active substances are released from the matrices exhibiting zero-order, near zero-order, or first-order release kinetics. Various parameters that could influence the release process, including glycerol content, glycerol domain size, or membrane thickness, are thoroughly investigated, elucidating guidelines for creating matrices capable of delivering the active substances at desired rates. Additionally, the composites proved to absorb significant amounts of liquid water (up to 1850% of sample mass), a feature that can be tuned by the manipulation of the composite structure.

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“…Gossypol is a natural product derived from the genus Gossypium , which is a phenolic aldehyde and acts as an inhibitor of various dehydrogenase enzymes [14]. Besides its putative contraceptive function, gossypol is a well-known antimalarial and a potential anticancer drug [15]. Recently, Saleh et al reported the critical role of gossypol in cell inflammation and oxidative stress [16].…”

Section: Introductionmentioning

confidence: 99%

Gossypol Promotes Bone Formation in Ovariectomy-Induced Osteoporosis through Regulating Cell Apoptosis

Liang

Chen

Liu

et al. 2018

BioMed Research International

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Osteoporosis is among the most common forms of age-related diseases, especially for females, which has been a grave public health problem. Drug therapies have shown promising outcomes to promote bone formation and bone density. This study identified a novel potential drug, gossypol, for the treatment of osteoporosis. Treatments of ovariectomy-induced osteoporosis mice with gossypol significantly increased serum osteocalcin and osteoprotegerin (OPG) levels; meanwhile they decreased serum RANKL levels. Microcomputed tomography (microCT) analysis showed that treatment of gossypol improved bone density and strength and decreased bone postyield displacement for both medullar and cortical bones. In vitro experiments also showed that gossypol increased cell viability in a time- and dose-dependent manner. Furthermore, incubation of the osteoblast MC3T3-E1 cells with gossypol inhibited cell apoptosis through intrinsic apoptotic pathway as evidenced by the Annexin V/PI assay, TUNEL assay, biochemical analysis, and western blot assays. Moreover, the classical Wnt/β-catenin signaling pathway was found to be regulated by gossypol treatments. Inhibition of Wnt/β-catenin signaling reversed the prevention effects of gossypol in osteoporosis. Our findings provided novel clues for the treatment of osteoporosis in clinic.

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Zero-Order Release of Gossypol Improves Its Antifertility Effect and Reduces Its Side Effects Simultaneously

Cited by 27 publications

References 40 publications

Hydrogen‐Bonded Films for Zero‐Order Release of Leuprolide

Hydrogen‐Bonded Films for Zero‐Order Release of Leuprolide

Glycerol–Silicone Elastomers as Active Matrices with Controllable Release Profiles

Gossypol Promotes Bone Formation in Ovariectomy-Induced Osteoporosis through Regulating Cell Apoptosis

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